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脊髓损伤后大鼠模型的微生物组改变和肠道炎症研究。

Investigation of Microbiota Alterations and Intestinal Inflammation Post-Spinal Cord Injury in Rat Model.

机构信息

1 Department of Biochemistry and Molecular Biology, University of Miami , Miller School of Medicine, Miami, Florida.

2 Miami Project to Cure Paralysis, Department of Neurological Surgery, University of Miami , Miller School of Medicine, Miami, Florida.

出版信息

J Neurotrauma. 2018 Sep 15;35(18):2159-2166. doi: 10.1089/neu.2017.5349. Epub 2018 Jun 7.

Abstract

Although there has been a significant amount of research focused on the pathophysiology of spinal cord injury (SCI), there is limited information on the consequences of SCI on remote organs. SCI can produce significant effects on a variety of organ systems, including the gastrointestinal tract. Patients with SCI often suffer from severe, debilitating bowel dysfunction in addition to their physical disabilities, which is of major concern for these individuals because of the adverse impact on their quality of life. Herein, we report on our investigation into the effects of SCI and subsequent antibiotic treatment on the intestinal tissue and microbiota. For that, we used a thoracic SCI rat model and investigated changes to the microbiota, proinflammatory cytokine levels, and bacterial communication molecule levels post-injury and gentamicin treatment for 7 days. We discovered significant changes, the most interesting being the differences in the gut microbiota beta diversity of 8-week SCI animals compared to control animals at the family, genus, and species level. Specifically, 35 operational taxonomic units were enriched in the SCI animal group and three were identified at species level; Lactobacillus intestinalis, Clostridium disporicum, and Bifidobacterium choerinum. In contrast, Clostridium saccharogumia was identified as depleted in the SCI animal group. Proinflammatory cytokines interleukin (IL)-12, macrophage inflammatory protein-2 (MIP-2), and tumor necrosis factor alpha were found to be significantly elevated in intestinal tissue homogenate 4 weeks post-SCI compared to 8-weeks post-injury. Further, levels of IL-1β, IL-12, and MIP-2 significantly correlated with changes in beta diversity 8-weeks post-SCI. Our data provide a greater understanding of the early effects of SCI on the microbiota and gastrointestinal tract, highlighting the need for further investigation to elucidate the mechanism underlying these effects.

摘要

尽管已经有大量研究集中在脊髓损伤 (SCI) 的病理生理学上,但关于 SCI 对远程器官的影响的信息有限。SCI 可以对多种器官系统产生重大影响,包括胃肠道。SCI 患者除了身体残疾外,经常患有严重的、使人衰弱的肠道功能障碍,这对这些人来说是一个主要问题,因为这对他们的生活质量有不利影响。在此,我们报告了我们对 SCI 及其随后的抗生素治疗对肠道组织和微生物群的影响的研究。为此,我们使用了胸 SCI 大鼠模型,并在损伤后和庆大霉素治疗 7 天后,研究了微生物群、促炎细胞因子水平和细菌通讯分子水平的变化。我们发现了显著的变化,最有趣的是,与对照组相比,8 周 SCI 动物的肠道微生物群β多样性在科、属和种水平上存在差异。具体而言,在 SCI 动物组中富集了 35 个操作分类单位,在物种水平上鉴定出 3 个;肠道乳杆菌、双歧杆菌和双歧杆菌。相比之下,在 SCI 动物组中发现梭菌 saccharogumia 被耗尽。4 周后,在 SCI 动物的肠道组织匀浆中发现白细胞介素 (IL)-12、巨噬细胞炎症蛋白-2 (MIP-2) 和肿瘤坏死因子 alpha 显著升高与损伤后 8 周相比。此外,IL-1β、IL-12 和 MIP-2 的水平与 8 周后 SCI 时β多样性的变化显著相关。我们的数据提供了对 SCI 对微生物群和胃肠道早期影响的更深入了解,强调需要进一步研究以阐明这些影响的机制。

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